Identification of copy number variants associated with BPES-like phenotypes.
Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.
Gijsbers
Antoinet C J
AC
Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S-6-P, Einthovenweg 20, 2333 CZ, Leiden, The Netherlands. a.c.j.gijsbers@lumc.nl
D'haene
Barbara
B
Hilhorst-Hofstee
Yvonne
Y
Mannens
Marcel
M
Albrecht
Beate
B
Seidel
Joerg
J
Witt
David R
DR
Maisenbacher
Melissa K
MK
Loeys
Bart
B
van Essen
Ton
T
Bakker
Egbert
E
Hennekam
Raoul
R
Breuning
Martijn H
MH
De Baere
Elfride
E
Ruivenkamp
Claudia A L
CA
D016569:Blepharophimosis / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D002869:Chromosome Aberrations; D005143:Eyelids / Q000002:abnormalities; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome